全文获取类型
收费全文 | 299篇 |
免费 | 46篇 |
国内免费 | 4篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 5篇 |
2019年 | 7篇 |
2018年 | 6篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 2篇 |
2014年 | 7篇 |
2013年 | 21篇 |
2012年 | 5篇 |
2011年 | 6篇 |
2010年 | 9篇 |
2009年 | 9篇 |
2008年 | 11篇 |
2007年 | 14篇 |
2006年 | 13篇 |
2005年 | 22篇 |
2004年 | 20篇 |
2003年 | 15篇 |
2002年 | 21篇 |
2001年 | 15篇 |
2000年 | 13篇 |
1999年 | 9篇 |
1998年 | 12篇 |
1997年 | 7篇 |
1996年 | 6篇 |
1995年 | 9篇 |
1994年 | 11篇 |
1993年 | 6篇 |
1992年 | 11篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有349条查询结果,搜索用时 15 毫秒
61.
Hydrophobic photolabeling as a new method for structural characterization of molten globule and related protein folding intermediates.
下载免费PDF全文
![点击此处可从《Protein science : a publication of the Protein Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
P. R. D''''Silva A. K. Lala 《Protein science : a publication of the Protein Society》1999,8(5):1099-1103
Recent advances in attempts to unravel the protein folding mechanism have indicated the need to identify the folding intermediates. Despite their transient nature, in a number of cases it has been possible to detect and characterize some of the equilibrium intermediates, for example, the molten globule (MG) state. The key features of the MG state are retention of substantial secondary structure of the native state, considerable loss of tertiary structure leading to increased hydrophobic exposure, and a compact structure. NMR, circular dichroism, and fluorescence spectroscopies have been most useful in characterizing such intermediates. We report here a new method for structural characterization of the MG state that involves probing the exposed hydrophobic sites with a hydrophobic photoactivable reagent--2[3H]diazofluorene. This carbene-based reagent binds to hydrophobic sites, and on photolysis covalently attaches itself to the neighboring amino acid side chains. The reagent photolabels alpha-lactalbumin as a function of pH (3-7.4), the labeling at neutral pH being negligible and maximal at pH 3. Chemical and proteolytic fragmentation of the photolabeled protein followed by peptide sequencing permitted identification of the labeled residues. The results obtained indicate that the sequence corresponding to B (23-34) and C (86-98) helix of the native structure are extensively labeled. The small beta-domain (40-50) is poorly labeled, Val42 being the only residue that is significantly labeled. Our data, like NMR data, indicate that in the MG state of alpha-lactalbumin, the alpha-domain has a greater degree of persistent structure than the beta-domain. However, unlike the NMR method, the photolabeling method is not limited by the size of the protein and can provide information on several new residues, for example, Leu115. The current method using DAF thus allows identification of stable and hydrophobic exposed regions in folding intermediates as the reagent binds and on photolysis covalently links to these regions. 相似文献
62.
Lipids in biological membrane fusion 总被引:8,自引:0,他引:8
The results reviewed suggest that membrane fusion in diverse biological fusion reactions involves formation of some specific intermediates: stalks and pores. Energy of these intermediates and, consequently, the rate and extent of fusion depend on the propensity of the corresponding monolayers of membranes to bend in the required directions.Proteins and peptides can control the bending energy of membrane monolayers in a number of ways. Monolayer lipid composition may be altered by different phospholipases [50, 85, 90], flipases and translocases [4, 50]. Proteins and peptides can change monolayer spontaneous curvature or hydrophobic void energy by direct interaction with membrane lipids [20, 32, 111]. Proteins may also provide some barriers for lipid diffusion in the plane of the monolayer [83, 141]. If diffusion of lipids at some specific membrane sites (e.g., in the vicinity of fusion protein) is somehow hindered, the energy of the bent fusion intermediates would reflect the elastic properties of these particular sites rather than the spontaneous curvature of the whole monolayers. Proteins may deform membranes while bringing them locally into close contact. The alteration of the geometric (external) curvature will certainly change the elastic energy of the initial state and, thus affect the energetic barriers of the formation of the intermediates [143]. In addition, the area and the energy of the stalk can be reduced by preliminary bending of the contacting membranes [111]. The possible effects of proteins and polymers on local elastic properties and local shapes of the membranes have been recently analyzed [22, 39, 45, 63]. These studies may provide a good basis for future development of theoretical models of protein-mediated fusion. 相似文献
63.
Huihua Sun Hongfang Zhang Ee Lui Ang Huimin Zhao 《Bioorganic & medicinal chemistry》2018,26(7):1275-1284
Biocatalysis has been increasingly used for pharmaceutical synthesis in an effort to make manufacturing processes greener and more sustainable. Biocatalysts that possess excellent activity, specificity, thermostability and solvent-tolerance are highly sought after to meet the requirements of practical applications. Generating biocatalysts with these specific properties can be achieved by either discovery of novel biocatalysts or protein engineering. Meanwhile, chemoenzymatic routes have also been designed and developed for pharmaceutical synthesis on an industrial scale. This review discusses the recent discoveries, engineering, and applications of biocatalysts for the synthesis of pharmaceuticals and pharmaceutical intermediates. Key classes of biocatalysts include reductases, oxidases, hydrolases, lyases, isomerases, and transaminases. 相似文献
64.
Phytochrome photoconversion 总被引:1,自引:1,他引:0
The spectral properties of native and modified phytochromes and the molecular events during phytochrome photoconversion, , are reviewed. Steady-state and time-resolved absorption spectra of native phytochrome A, as well as recombinant phytochromes (oat and potato phytochrome A and potato phytochrome B) reconstituted with phycocyanobilin and phytochromobilin as chromophores, are analysed. The vinyl double bond, present at position 18 in phytochromobilin and substituted by an ethyl group in phycocyanobilin, has a considerable influence on the photo-transformation kinetics of phytochromes A and B, evidently due to a strong interaction of this region of the chromophore with the protein surrounding. The kinetics of the phototransformation of potato phytochrome B differs from that of oat phytochrome A (wild-type and recombinant), indicating that the chromophore-protein interaction in phytochrome B is different from that in phytochrome A. It remains to be seen whether this difference is due to the di- versus monocotyledon origin of the phytochromes. Optoacoustic spectroscopy, applied to native oat phytochrome A, afforded thermo-dynamic, structural and kinetic parameters of the Pr→I700 and the I700→Pr phototransformations. Raman and infrared spectroscopic data for wild-type phytochrome A suggest that the protonated chromophore in Pr undergoes torsions around two single bonds in addition to the Z→E isomerization of the 15 ,16 double bond, and that all transients, possibly with the exception of IbI, are protonated at the central pyrrole ring. 相似文献
65.
Shrutee Jakhanwal Chung‐Tien Lee Henning Urlaub Reinhard Jahn 《The EMBO journal》2017,36(12):1788-1802
Assembly of the SNARE proteins syntaxin1, SNAP25, and synaptobrevin into a SNARE complex is essential for exocytosis in neurons. For efficient assembly, SNAREs interact with additional proteins but neither the nature of the intermediates nor the sequence of protein assembly is known. Here, we have characterized a ternary complex between syntaxin1, SNAP25, and the SM protein Munc18‐1 as a possible acceptor complex for the R‐SNARE synaptobrevin. The ternary complex binds synaptobrevin with fast kinetics, resulting in the rapid formation of a fully zippered SNARE complex to which Munc18‐1 remains tethered by the N‐terminal domain of syntaxin1. Intriguingly, only one of the synaptobrevin truncation mutants (Syb1‐65) was able to bind to the syntaxin1:SNAP25:Munc18‐1 complex, suggesting either a cooperative zippering mechanism that proceeds bidirectionally or the progressive R‐SNARE binding via an SM template. Moreover, the complex is resistant to disassembly by NSF. Based on these findings, we consider the ternary complex as a strong candidate for a physiological intermediate in SNARE assembly. 相似文献
66.
From lignins to tannins: forty years of enzyme studies on the biosynthesis of phenolic compounds 总被引:1,自引:0,他引:1
Gross GG 《Phytochemistry》2008,69(18):3018-3031
In the early 1960s, enzyme studies increasingly began to replace the common ‘feeding’ experiments in which labeled tracers were applied to living plants or plant parts for elucidating metabolic pathways. This advanced technique allowed to gain much deeper insights into individual details of metabolic sequences, and particularly on the previously inaccessible role of activated ‘energy-rich’ intermediates. Based on the author’s own experience for the past 40+ years in this field, principal findings and trends elucidating the pathways to lignin and lignin precursors, acyl amides and hydrolyzable tannins (gallotannins, ellagitannins) by enzyme studies are reported. 相似文献
67.
68.
Isao Sakane Kunihiro Hongo Tomohiro Mizobata Yasushi Kawata 《Protein science : a publication of the Protein Society》2009,18(1):252-257
It is difficult to determine the structural stability of the individual subunits or protomers of many proteins in the cell that exist in an oligomeric or complexed state. In this study, we used single‐molecule force spectroscopy on seven subunits of covalently linked cochaperonin GroES (ESC7) to evaluate the structural stability of the subunit. A modified form of ESC7 was immobilized on a mica surface. The force‐extension profile obtained from the mechanical unfolding of this ESC7 showed a distinctive sawtooth pattern that is typical for multimodular proteins. When analyzed according to the worm‐like chain model, the contour lengths calculated from the peaks in the profile suggested that linked‐GroES subunits unfold in distinct steps after the oligomeric ring structure of ESC7 is disrupted. The evidence that structured subunits of ESC7 withstand external force to some extent even after the perturbation of the oligomeric ring structure suggests that a stable monomeric intermediate is an important component of the equilibrium unfolding reaction of GroES. 相似文献
69.
Ashish K. Patra 《Journal of molecular biology》2009,389(4):759-2444
The modulation of the folding mechanism of the small protein single-chain monellin (MNEI) by the Escherichia coli chaperone GroEL has been studied. In the absence of the chaperone, the folding of monellin occurs via three parallel routes. When folding is initiated in the presence of a saturating concentration of GroEL, only 50-60% of monellin molecules fold completely. The remaining 40-50% of the monellin molecules remain bound to the GroEL and are released only upon addition of ATP. It is shown that the basic folding mechanism of monellin is not altered by the presence of GroEL, but that it occurs via only one of the three available routes when folding is initiated in the presence of saturating concentrations of GroEL. Two pathways become nonoperational because GroEL binds very tightly to early intermediates that populate these pathways in a manner that makes the GroEL-bound intermediates incompetent to fold. This accounts for the monellin molecules that remain GroEL-bound at the end of the folding reaction. The third pathway remains operational because the GroEL-bound early intermediate on this pathway is folding-competent, suggesting that this early intermediate binds to GroEL in a manner that is different from that of the binding of the early intermediates on the other two pathways. It appears, therefore, that the same protein can bind GroEL in more than one way. The modulation of the folding energy landscape of monellin by GroEL occurs because GroEL binds folding intermediates on parallel folding pathways, in different ways, and with different affinities. Moreover, when GroEL is added to refolding monellin at different times after commencement of refolding, the unfolding of two late kinetic intermediates on two of the three folding pathways can be observed. It appears that the unfolding of late folding intermediates is enabled by a thermodynamic coupling mechanism, wherein GroEL binds more tightly to an early intermediate than to a late intermediate on a folding pathway, with preferential binding energy being larger than the stability of the late intermediate. Hence, it is shown that GroEL can inadvertently and passively cause, through its ability to bind different folding intermediates differentially, the unfolding of late productive intermediates on folding pathways, and that its unfolding action is not restricted solely to misfolded or kinetically trapped intermediates. 相似文献
70.
Melanie J. StablesDerek W. Gilroy 《Progress in lipid research》2011,50(1):35-51
Originally regarded as just membrane constituents and energy storing molecules, lipids are now recognised as potent signalling molecules that regulate a multitude of cellular responses via receptor-mediated pathways, including cell growth and death, and inflammation/infection. Derived from polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), each lipid displays unique properties, thus making their role in inflammation distinct from that of other lipids derived from the same PUFA. The diversity of their actions arises because such metabolites are synthesised via discrete enzymatic pathways and because they elicit their response via different receptors. This review will collate the bioactive lipid research to date and summarise the findings in terms of the major pathways involved in their biosynthesis and their role in inflammation and its resolution. It will include lipids derived from AA (prostanoids, leukotrienes, 5-oxo-6,8,11,14-eicosatetraenoic acid, lipoxins and epoxyeicosatrienoic acids), EPA (E-series resolvins), and DHA (D-series resolvins, protectins and maresins). 相似文献